Compared to microcrystalline cellulose and cellulosic derivatives, such as ethers and esters that are widely used in the cosmetic and pharmaceutical industries, oxidized celluloses have received relatively little attention. The various applications of oxidized celluloses (or oxycelluloses, as they are often called) in medical and related areas include their use as: (1) coating materials for ferric and aluminum salt granules in the formulation of microencapsulated astringent hemostatic agents; (2) bodying agents in the preparation of cosmetic and pharmaceutical preparations; (3) biocompatible antihemorrhegic absorbable materials for wounds and to stop bleeding during surgery; (4) fibrin formation-accelerating agents; (5) deodorants for absorbent pads (e.g., dressing, diapers and catamenials); and (6) biocompatible mold release agents or donning powders and medical lubricants for surgical gloves, and the like. However, the continuing lack of the wide-spread use of oxycelluloses as a pharmaceutical aids can be attributed to the unavailability of methods to produce oxycelluloses that are stable during storage at room temperature and at elevated temperatures, and are compatible with a wide variety of chemicals.
Several strategies have been developed for the preparation of oxycelluloses from cellulosic materials using a variety of oxidants. These oxidants include gaseous oxygen, hydrogen peroxide, peracetic acid, chlorine dioxide, nitrogen dioxide and/or dinitrogen tetraoxide, persulfates, permanganate, dichromatesulfuric acid, and alkali or alkaline earth metal hypohalites or periodates. [T. P. Nevell, in Cellulose Chemistry and its Applications: 1, Cellulose, T. P. Nevell et al., eds., Ellis Horwood Ltd., England (1985) at Ch. 10.] Of these, oxycelluloses prepared utilizing alkali metal periodates, nitrogen dioxide, gaseous oxygen, hydrogen peroxide, and alkali or alkaline earth metal hypohalites have been extensively studied. The periodate-derived oxycelluloses are extremely sensitive to alkali and undergo condensation and other reactions characteristic of aldehyde functional groups.
The oxycellulose products, prepared using nitrogen dioxide and/or dinitrogen tetraoxide in the liquid or gaseous state, are also very sensitive to alkali, and have a high free carboxylic acid content. The latter have been reported to cause gradual deterioration and color change of the product during storage. According to German Patent No. 2,061,796, the room temperature stability of the nitrogen oxide-derived oxycellulose can be improved by treating the product with alkali metal borohydride in an aqueous-alcohol medium, followed by washing the solid with dilute acid, drying, and sterilization.
U.S. Pat. No. 3,364,200 discusses the production of stable nitrogen oxide and/or dinitrogen tetraoxide-derived oxidized cellulose by washing the product first with a non-aqueous solvent (carbon tetrachloride or tetrachlorodifluoroethane), then with an aqueous-alcohol solution, and finally with a non-aqueous solvent having an affinity for water. The oxidation of cellulose by gaseous oxygen and/or hydrogen peroxide, in the presence of alkali, has been reported to produce oxycelluloses that have a high amount of ketone groups and some aldehyde and carboxylic acid groups. Studies have reported that this method is highly non-reproducible, probably due to the strong catalytic effect of the metal ions present in the water used as the reaction medium. It is practically impossible to completely eliminate such ions or to assure their presence, in precisely the same amounts, in consecutive experiments. The hypochlorite-oxycelluloses, prepared under mild acidic conditions, are known to degrade and turn yellow during storage, whereas products prepared using alkaline solutions are quite stable. See T. P. Nevell, in Cellulose Chemistry and its Applications: 1. Cellulose, T. P. Nevell et al., eds., Ellis Horwood Ltd., England (1985) at Ch. 10.
U.S. Pat. No. 4,480,089 (Chen) discusses the preparation of a cellulose product suitable for use in cosmetics or pharmaceuticals using an excess of hypochlorite solution, having an initial pH of about 12, at various temperatures, and by allowing the pH of the reaction solution to drop to as low as about 2. The tendency of the product to undergo color changes during storage is not mentioned. Other methods used to prepare oxycelluloses include oxidation of cotton linters with a HNO.sub.3 --NaNO.sub.2 mixture, followed by controlled heterogenous hydrolysis, or by stabilization and sterilization, or by oxidation with an acidic K.sub.2 Cr.sub.2 O.sub.7 --NO.sub.2 mixture.
The first use of persulfate in the oxidation of cellulose was reported by Ditz, J. Prakt. Chem., 78, 343 (1908). Since then, very little work has been reported. According to F. H. Chowdhury et al., Sci. Res., 3, 22 (1966), oxidation of cellulose by persulfate can be achieved in neutral or acidic medium only in the presence of traces of silver ions.
I. Rusznak et al., Kolorisztikai Ertesito, 10, 38 (1968) and A. Kantruch et al., Kolorisztikai Ertesito, 10, 208 (1968) discuss the reaction of .alpha.-cellulose with aqueous sodium persulfate for 1-10 hours at 50.degree.-70.degree. C. at pH 4-10, using a persulfate concentration of 0.025M, 0.05M, 0.1M or 0.15M and .alpha. weight-to-volume ratio of 1:100 .alpha.-cellulose:sodium persulfate solution. However, neither method appears to produce oxycellulose products suitable for use in pharmaceutical preparations, but yield instead unruptured or long fibers, with a low surface area. These fibers do not disperse in water and do not coalesce.
Therefore, there appears to be an unfilled need for a method to oxidize cellulosic materials to oxycellulosic products which can serve as carriers for a wide variety of bioactive materials in substantive, controlled and/or sustained release formulations.